This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite ongoing control and prevention efforts, malaria remains one of the most devastating infectious diseases, world-wide. Female Anopheles mosquitoes are the carriers (vectors) for human malaria. When a mosquito bites an infected individual, it takes up infectious forms of the malaria parasite along with blood. The parasite undergoes a complex journey through its mosquito vector, before it can subsequently be injected into the next human host via mosquito bite. As part of this journey, the parasite must cross the linings (epithelia) of two mosquito organs, the midgut and the salivary glands. Both crossing events are central to the successful development of the parasite within the mosquito. This study aims to gain insight into how these mosquito epithelia react and potentially limit malaria parasite infection in the natural parasite/vector combination that most important to human health: the African malaria mosquito, Anopheles gambiae and the human malaria parasite, Plasmodium falciparum. The specific hypothesis of this project is that An. gambiae midgut and salivary glands mount a common immune response against parasite invasion, which is characterized by serpin-6 (SRPN6), a protein that functions as a serine protease inhibitor. Our aims are to (a) explore the regulation of SRPN6 during the invasion of the midgut and salivary glands by the parasite and (b) to measure any potential effect of SRPN6 on the passage of the parasite through these epithelia. The results of this study can provide important clues to the potential contribution of epithelial immunity to parasite transmission by mosquito vectors in a disease-relevant mosquito/parasite combination. Such knowledge could potentially be used to design novel malaria intervention strategies, in which the parasite transmission cycle in the mosquito.